Photo-oxidative stress down-modulates the activity of nuclear factor- κB via involvement of caspase-1, leading to apoptosis of photoreceptor cells

Raghu Krishnamoorthy, Matthew J. Crawford, Madan M. Chaturvedi, Sushil K. Jain, Bharat B. Aggarwal, Muayyad R. Al-Ubaidi, Neeraj Agarwal

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The mechanisms of photoreceptor cell death via apoptosis, in retinal dystrophies, are largely not understood. In the present report we show that visible light exposure of mouse cultured 661W photoreceptor cells at 4.5 milliwatt/cm2 caused a significant increase in oxidative damage of 661W cells, leading to apoptosis of these cells. These cells show constitutive expression of nuclear factor-κB (NF-κB), and light exposure of photoreceptor cells results in lowering of NF-κB levels in both the nuclear and cytosolic fractions in a time-dependent manner. Immunoblot analysis of IκBα and p50, and p65 (RelA) subunits of NF-κB, suggested that photo- oxidative stress results in their depletion. Immunocytochemical studies using antibody to RelA subunit of NF-κB further revealed the presence of this subunit constitutively both in the nucleus and cytoplasm of the 661W cells. Upon exposure to photo-oxidative stress, a depletion of the cytoplasmic and nuclear RelA subunit was observed. The depletion of NF-κB appears to be mediated through involvement of caspase-1. Furthermore, transfection of these cells with a dominant negative mutant IκBα greatly enhanced the kinetics of down modulation of NF-κB, resulting in a faster photo-oxidative stress- induced apoptosis. Taken together, these studies show that the presence of NF-κB RelA subunit in the nucleus is essential for protection of photoreceptor cells against apoptosis mediated by an oxidative pathway.

Original languageEnglish
Pages (from-to)3734-3743
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number6
DOIs
StatePublished - 5 Feb 1999

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